The bulk of non-lysosomal intracellular proteolysis is performed by a large 700 kDa complex known as the proteasome. The proteasome is recruited to produce peptides for display on MHC class 1 molecules by a heptameric 200 kDa complex known as REG, which binds to both ends of the proteasome to form a 1.1 MDa activated complex. We are currently determining the crystal structures of proteasome-REG complexes and of complexes with various inhibitors that mimic the binding of substrate at the proteasome active sites. The high intensity of synchrotron radiation is essential for these projects because the crystals are small and diffract very weakly with a rotating anode source. Other ongoing projects are aimed at structure determination of various protein structures that are relevant for HIV architecture, intracellular proteolysis, or heme biosynthesis.